AITL patient with incidental rare splenic vascular tumor

Authors of the case:
MD Consultant Pathologist Ugnius Mickys; MD Consultant Pathologist Julius Drachneris; Resident doctor Gintarė Ražanskienė
45-year-old male was admitted to the hematology center due to leukopenia (1,02 *109/l), thrombocytopenia (62*109/l) and splenomegaly (22 cm). Trephine biopsy and subsequent lymph node biopsies revealed angioimmunoblastic T-cell lymphoma, therefore chemotherapy with cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP) was commenced. Patient underwent 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan for initial staging and treatment response which revealed splenomegaly without focal elevated uptake lesions in the spleen. The decision was made to perform a splenectomy due to the hypersplenism.
Operative specimen contained a large spleen, measuring 21x13x8 cm, weighing 1309 g and accessory spleen, measuring 2,4x2,3x1,8 cm. Both large spleen and accessory spleen had an uneven, nodular capsular surface (Fig.1). On the cut surface parenchyma was diffusely altered, with multiple branching cystic spaces up to 1,4 cm (Fig.2). 
Microscopic examination revealed a tumor with nodular architecture between intervening residual splenic parenchyma, composed of erythrocytes-filled vascular channels and cystic vascular spaces (Fig.3). Vascular channels were lined with plump cells with bland, oval to indented nuclei and eosinophilic cytoplasm. The cells were “peeling off” into the lumina (Fig.4) and focally showing hemophagocytosis (Fig.5).  
Tumors cells showed dual positivity for endothelial and histiocytic immunohistochemical markers. Except for CD34, tumor cells showed diffuse positivity for other vascular markers such as CD31, ERG, FLI1 and vWF (Fig.6-9). Tumors cells were also positive for CD68, CD163, CD4, langerin, lysozyme and complement receptor CD21 (Fig.10-14).  Specific marker for splenic sinusoid - CD8 was negative in tumor cells (Fig.15). Also negative were Asm Actin and HHV8. Ki-67 proliferative index was 5-10 % (Fig.16).
Moreover, all of the 11 lymph nodes, found in splenic hilum, were positive for vascular tumor metastasis (Fig.17). Additionally, the residual tissue of lymph nodes showed polymorphous  T-cell infiltrate with T follicular helper immunophenotype (PD1/ICOS+), explained by prior diagnosis of angioimmunoblastic T cell lymphoma (Fig.18-19). 
Final diagnosis was littoral cell hemangioendothelioma seu low-grade littoral cell angiosarcoma, due to the lymph node metastasis without other markers of malignant potential, such as solid growth, necrosis, high mitotic index and cytologic atypia.
5 months after the splenectomy there is no evidence of vascular tumor progression.  Patient white blood cells is within normal range (5,98 *109/l), thrombocytopenia has also significantly improved (132*109/l). The patient received a second-line chemotherapy and is now waiting for allogeneic stem cell transplantation.
Littoral cell tumors are rare vascular neoplasms exclusively found in spleen, composed of a specific type of cells with both endothelial and histiocytic qualities. Littoral cells line sinuses of the red pulp in a normal spleen and belong to the reticuloendothelial cell system.  Most of the littoral cell tumors are angiomas with benign and indolent clinical course, commonly found incidentally.  Only sparse case reports of metastatic littoral cell tumors can be found in English literature. These tumors are called littoral cell hemangioendothelioma or low-grade littoral cell angiosarcoma. In fact, there is no definite distinction between these two terms. In a review of 180 cases of splenic littoral cell tumors by Sarandria et al, spleen size of  > 20 cm in length preoperatively, weighing > 1500 g  was significantly associated with malignant behavior. In this present case the spleen preoperatively was 22 cm in length. Interestingly, the patient claimed that splenomegaly was observed since childhood, which might prove the indolent course of the disease. Histological markers, associated with malignant behavior, noted in metastatic littoral cell tumors are solid growth pattern, necrosis and high mitotic index. However, none of the aforementioned features were seen in the current case. 
In spite of distinct microscopic appearance of bland hobnail cells, lining vascular channels, littoral cell tumors might cause diagnostic challenges and should be differentiated from other splenic  vascular neoplasms, such as splenic hamartoma and primary splenic angiosarcoma. 
Splenic hamartoma has a distinct immunophenotype with maintained expression of CD8 - specific marker for splenic sinusoids and negativity for histiocytic (CD68) and complement receptor (CD21) markers.
Primary splenic angiosarcoma aside from endothelial markers can also express some histiocytic markers such as CD68 and lysozyme. However, it is usually negative for CD21 and positive for CD34, contrary to littoral cell tumors. Also, contrary to primary splenic angiosarcoma, metastatic littoral cell tumors show relatively indolent behavior. Larsen et al. hypothesise that low-grade littoral cell angiosarcoma clinically, morphologically and immunophenotypically has more incommon with low-grade histiocytic sarcoma than angiosarcoma or hemangioendothelioma. While classification of rare histiocytic neoplasm is still evolving, we might one day consider low-grade littoral cell angiosarcoma as a type of histiocytic sarcoma.
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